We will investigate micrometer-sized structural changes in the lung of small living animals (newborn to adult mice and/or rats younger than 21-28 days), opening up a completely new field of investigation in lung developmental and lung disease processes. To this end we will develop an imaging platform consisting in the combination of ventilation-triggered ultrafast, synchrotron-based tomographic microscopy from one hand and on-line image registration and high-speed reconstruction from the other hand.

Little is known about the structural alteration taking place in the gas-exchange area during breathing cycles. Does a heterogeneous distension [1] or an opening-and-collapse of alveoli take place [2]? What is the role of the acini, the functional units of the gas-exchange area (an acinus is defined as the area which is fed by one airway of the last (most distal) generation of purely conducting airways)? These questions are either on debate or completely open.

We would like to study the structural alteration taking place in the acini during different kinds of breathing cycles and during mechanical ventilation. In addition, we would like to study the mechanical damage which occurs during ventilation due to an overextension of the lung (volume- and barotrauma) [3].

Until now the recruitment of alveoli was typically studied at subpleural alveoli, because, due to technical limitations, only the lung surface was accessible [1,2,4]. Unfortunately, these alveoli possess an atypical shape and it may be that they are not representative for the entire lung. The application of ultrafast synchrotron-based tomographic microscopy will enable us to study alveolar recruitment in-vivo in an entire lung and, more important, in individual acini.

We would like to point out that the instrumentation developed during this program will find applications also beyond the specific biological question suggested so far. Namely, ultrafast 3D tomographic microscopy is the tool needed when studying rapidly evolving system (like foams) or dynamical processes (like micro-vascular flows), as well described by the review of Fouras et al. [5].